Most squamous cell carcinomas of the head and neck (HNSCC) overexpress ERBB1/EGFR, but EGF receptor (EGFR)-targeted therapies have yielded disappointing clinical results in treatment of this cancer. Here, we describe a novel interaction between EGFR and the ligand EphrinB1 (EFNB1), and we show that EFNB1 phosphorylation and downstream signaling persists in the presence of cetuximab. Mechanistically, cetuximab drives a shift in EGFR dimerization partners within the signaling complex, suggesting… CONTINUE READING